Dietary lipids and sweeteners regulate glucagon - like 1 peptide - 2 secretion 2

18 Glucagon-like peptide-2 (GLP-2) is a potent intestinal growth factor derived from 19 enteroendocrine L-cells. Although food intake is known to increase GLP-2 secretion, its 20 regulatory mechanisms are largely unknown owing to its very short half-life in venules. The 21 aims of this study were to compare the effects of luminal nutrients on the stimulation of 22 GLP-2 secretion in vivo using lymph samples and to clarify the involvement of the sweet 23 taste receptor in this process in vitro. Lymph samples were collected from the thoracic duct 24 after bolus administration of dietary lipids or sweetening agents into the duodenum of rats. 25 Human enteroendocrine NCI-H716 cells were also used to compare the effects of various 26 nutrients on GLP-2 secretion. GLP-2 concentrations were measured by ELISA in vivo and in 27 vitro. GLP-2 secretion was enhanced by polyunsaturated fatty acid (PUFA) and 28 monounsaturated fatty acid (MUFA)-rich dietary oils, dietary carbohydrates, and some 29 kinds of sweeteners in rats; this effect was reproduced in NCI-H716 cells using 30 alpha-linolenic acid (αLA), glucose, and sweeteners. GLP-2 secretion induced by sweetening 31 agents was inhibited by lactisole, a sweetness-antagonizing inhibitor of T1R3. In contrast, 32 lactisole was unable to inhibit GLP-2 secretion induced by αLA alone. Our results suggested 33 that fatty acidand sweetener-induced GLP-2 secretion may be mediated by 2 different 34 pathways, with the sweet taste receptor involved in the regulation of the latter. 35 36